PB2516: ACTIGRAPHY IMPROVEMENT WITH VOXELOTOR (ACTIVE) STUDY: IMPACT OF VOXELOTOR ON PHYSICAL ACTIVITY, FATIGUE, AND SLEEP QUALITY
Authors: Nirmish Shah, Clark Brown, Biree Andemariam, Modupe Idowu, Alexander Glaros, Robert M. Cronin, Barbara Moehring, Carolyn Hoppe, Sandy Dixon, Brooke Hayward, David M. Purdie, Emily Reihm Meier, Deepa Manwani
Journal: HemaSphere (2023)

Topic: 26. Sickle cell disease Background: People with sickle cell disease (SCD) experience pain, sleep disturbance, poor sleep quality, fatigue, decreased exercise capacity, and decreased quality of life (QOL). Children with SCD are less physically active than their peers without SCD, with an observed association between sedentary behavior and more-severe anemia. Voxelotor is a sickle hemoglobin polymerization inhibitor approved in the United States and the United Arab Emirates for the treatment of SCD in patients aged ≥4 years and has marketing authorization in the European Union, Great Britain, Oman, and Kuwait for patients aged ≥12 years. Voxelotor has been shown to increase hemoglobin (Hb) and reduce markers of hemolysis; however, its impact on QOL has not been fully captured. Aims: To examine the effects of voxelotor on physical activity, fatigue, and sleep quality in patients with SCD participating in the open-label, multicenter, phase 4 ActIVe study (NCT04400487). Methods: Participants aged 12 to 55 years with SCD and chronic anemia (Hb ≤8.0 g/dL at screening) received voxelotor 1500 mg for 24 weeks. Hb was measured at baseline and weeks 2, 12, and 24. Wrist-worn actigraphy devices were used to continuously assess activity level and sleep from baseline through week 24 and were required to be worn for 18 hours/day for ≥8 days during each 2-week period. Patient-reported outcomes were evaluated using the National Institutes of Health Patient-Reported Outcome Measurement Information System 43 (PROMIS-43) for adults (aged >17 years) and PROMIS-37 for adolescents (aged ≤17 years); responses deemed meaningful were interpreted at the group level as a ≥5-point change from baseline (CFB) in PROMIS domains. Informed consent/assent was collected from all participants. Results: A total of 25 patients were enrolled across 10 US sites, with a mean (SD, range) age of 25.0 (12.05, 12-51) years; 64% were female, and 92% were Black or African American. Patients were treated with voxelotor for a median (range) duration of 22.3 (2.4-25.7) weeks. At week 24, mean (SD) CFB in Hb was 0.72 (1.21) g/dL (n=23); 23 of 25 patients (92%) showed an increase in Hb at some point in this study. CFB in moderate or vigorous activity (defined as ≥3 metabolic equivalents of task) over 22 weeks is shown in the Figure, with a median numerical increase of 13.6 min/day (17.0%) at weeks 20 to 22 (n=17 patients who compliantly wore the actigraphy device). The median percentage CFB in total daily physical activity at weeks 20 to 22 was +3.8%. Total wake time after sleep onset numerically decreased, with a mean (SD) CFB of –9.9 (47.12) min/day (–2.0% [37.8%]) at weeks 20 to 22. In the 11 adults who completed PROMIS measures at week 24, clinically meaningful CFB values for fatigue (mean CFB [SD] of –6.9 [5.86]; 6/11 patients with ≥5-point CFB) and pain interference (mean CFB [SD] of –5.7 [5.66]; 6/11 with ≥5-point CFB) were observed. In addition, 4/11 patients had a ≥5-point decrease in sleep disturbance (mean CFB [SD] of –1.9 [8.06]). Summary/Conclusion: Results from the ActIVe study suggest that voxelotor-treated patients may experience improved QOL, including increased physical activity, reduced fatigue, and reduced wake time after sleep onset. The study was limited by the small number of participants, a low response rate to QOL questionnaires, and variability in use of the wrist-worn actigraphy device. Additional studies are needed to further examine the effects of voxelotor on QOL, including physical activity and sleep quality. Funding: Pfizer Inc.Keywords: Sickle cell disease, Quality of life, Fatigue